Analysis of the MCL-1 gene in Chinese women with idiopathic premature ovarian insufficiency

Abstract

Objective

Animal studies have demonstrated that myeloid cell leukemia-1 (Mcl-1) gene deficiency leads to premature ovarian failure and decreased reproductive ability in mice. This study investigated the relationship between MCL-1 gene variation and idiopathic premature ovarian insufficiency (POI) in Chinese women.

Methods

A total of 200 idiopathic POI patients and 100 healthy controls were recruited for this study, and peripheral blood was collected. First, genomic DNA was extracted from peripheral leukocytes. Then, the entire coding region and splice sites of the MCL-1 gene were amplified by polymerase chain reaction. Chi-squared tests were used to compare the genotype distribution and allele frequency of single nucleotide polymorphisms between the POI and control groups.

Results

Three mutations of the MCL-1 gene (c.–36C > T, c.–131C > T and c.78C > T) were identified. After data analysis, c.–36C > T and c.–131C > T in the 5′-untranslated region were both found in the POI group and the control group. No difference was found in the genotype distribution or allelic frequency of either variant between the POI group and the control group (p > 0.05). The synonymous variant (c.78C > T) in exon 1 was discovered in only one of the control subjects and did not result in a change in amino acid sequence (p.Gly26Gly).

Conclusion

MCL-1 gene mutation may not be associated with idiopathic POI in Chinese women.

中国女性特发性早发性卵巢功能不全的MCL-1基因分析 摘要

目的：动物研究表明, Mcl-1基因缺陷导致小鼠卵巢早衰和生殖能力下降。本研究调查了中国女性 MCL-1 基因变异与早发性卵巢功能不全（POI）之间的关系。

方法：本研究共招募200名早发性卵巢功能不全患者和100名健康对照者, 采集外周血。首先, 从外周白细胞中提取基因组 DNA。然后, 通过聚合酶链反应扩增 MCL-1 基因的整个编码区和剪接位点。卡方检验用于比较 POI 组和对照组之间单核苷酸多态性的基因型分布和等位基因频率。

结果：鉴定了 MCL-1 基因的三个突变（c.–36C> T、c.–131C > T 和 c.78C > T）。经数据分析, POI组和对照组均发现5ʹ-非编码区的c.–36C>T和c.–131C>T。POI 组和对照组之间所有变体的基因型分布和等位基因频率均未发现差异（p > 0.05）。外显子 1 中的同义变体 (c.78C> T) 仅在一名对照受试者中发现, 并没有导致氨基酸序列 (p.Gly26Gly) 发生变化。

结论： MCL-1基因突变可能与中国女性特发性POI无关。

Keywords:

• Premature ovarian insufficiency
• myeloid cell leukemia-1
• mutation

Acknowledgements

The authors thank all of the subjects for their participation in this research.

Potential conflict of interest

No potential conflict of interest was reported by the authors.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This study was supported by a project funded by National Natural Science Foundation of China [Grant No. 81771540], [Grant No. 81401175]; Jiangsu Province Medical Innovation Team [Grant No. CXTDA2017004]; Jiangsu Province Maternal and Children Project [Grant No. FXK201701], [Grant No. FRC201701], [Grant No. QNRC2016611]; the Priority Academic Program Development of Jiangsu Higher Education Institutions.